DOI: 10.1111/j.1744-4667.2011.00076.x The Obstetrician & Gynaecologist http://onlinetog.

org

2012;14:1724

Review

HIV in pregnancy: an international perspective

Laura Byrne MRCP,a, Ade Fakoya FRCP,b Kate Harding FRCOGc
Specialty Registrar in Genitourinary & HIV Medicine, Ambrose King Centre, The Royal London Hospital, Turner Street, London E1 1BB, UK Honorary Senior Research Fellow, Primary Care & Population Health, Faculty of Population Health Sciences, University College London, Gower Street, London WC1E 6BT, UK c Consultant Obstetrician, Department of Obstetrics, St Thomas Hospital, Westminster Bridge Road, London SE1 7EH, UK Correspondence: Laura Byrne. Email: laura.byrne@bartsandthelondon.nhs.uk
b a

Key content:

r The HIV epidemic continues to be a major challenge to global r Mother to child transmission accounts for 90% of HIV infections r Transmission of HIV from mother to child is largely preventable. r The implementation of interventions to prevent mother to child r Prevention of mother to child transmission of HIV in the

Objectives:

r To outline the interventions that have been shown to reduce

health.

in childhood.

mother to child transmission of HIV in both the developed and developing worlds. r To discuss the challenges in the prevention of mother to child transmission faced by the international community.
Ethical issues:

transmission of HIV has been successful in the developed world. developing world is limited by resources, lack of infrastructure and stigma.

r Should we take cost into account when writing guidelines for

preventing mother to child transmission of HIV in resource-poor settings?

Keywords highly active antiretroviral therapy / HIV testing / infant

feeding / mother to child transmission / short-term antiretroviral therapy

Please cite this paper as: Byrne L, Fakoya A, Harding K. HIV in pregnancy: an international perspective. The Obstetrician & Gynaecologist 2012;14:1724.

Introduction
The HIV epidemic continues to be a major challenge for global health. The latest figures published by the World Health Organization (WHO)1 show that there are 34 million people living with HIV and 2.02 million of these are children under the age of 15 who require antiretroviral therapy. In 2010 there were 390 000 new HIV infections in children and over 90% of these were acquired by mother to child transmission.1 The HIV epidemic has also had a negative impact on maternal mortality rates, especially in Eastern and Southern Africa.2 Globally, HIV/AIDS is now the leading cause of mortality among women of reproductive age and in several high-prevalence countries, such as South Africa and Zimbabwe, HIV is the leading cause of maternal mortality.3 The challenges in the prevention of mother to child transmission centre on scaling up services to meet the current recommendations of universal antenatal testing in areas of high HIV prevalence and antiretroviral therapy for all HIVpositive pregnant women. Access to antenatal care is variable in resource-limited countries. While 98% of pregnant women in high-income countries report at least one antenatal visit with a skilled health worker, this figure is at most 68% in the developing world (range 28100%).4 In resource-limited

settings only 35% of pregnant women receive an HIV test and 48% of HIV-positive pregnant women receive effective antiretroviral therapy to prevent mother to child transmission, although this is a significant improvement on the 10% in 2004.1, 5 In resource-rich countries, the implementation of multiple evidence-based interventions has reduced mother to child transmission of HIV to very low levels. The mother to child transmission rate in the UK is 1.2% overall and 0.8% in women who have been on antiretroviral therapy for at least the last 2 weeks of their pregnancy.6 To reduce the number of children infected or affected by HIV, the WHO and Joint United Nations Programme on HIV/AIDS (UNAIDS) have proposed a comprehensive approach consisting of four main strategies:5 1 Primary prevention of HIV among women of childbearing age 2 Preventing unintended pregnancies among women living with HIV 3 Preventing HIV transmission from women living with HIV to their infants 4 Providing appropriate treatment, care and support to mothers living with HIV and their children and families.

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HIV in pregnancy: an international perspective

This article focuses on the interventions that are effective in addressing the third strategy:

Box 1. Factors associated with risk of mother to child transmission of HIV

r r r r

antenatal HIV testing antiretroviral therapy during pregnancy, labour and the postnatal period optimal management of labour and delivery support of infant feeding choice.

Increased risk High maternal HIV viral load Low maternal CD4 count Low weight for gestational age Chorioamnionitis Concurrent maternal sexually transmitted infection

We review both the guidance in the UK and guidance from WHO, which is intended primarily for resource-limited countries.

Decreased risk Low maternal HIV viral load Antiretroviral therapy during pregnancy Elective caesarean section Avoidance of breastfeeding

Timing and factors affecting mother to child transmission of HIV

Transmission rates in untreated non-breastfeeding populations in resource-rich countries range from 1432%, compared with 2548% among breastfeeding populations in resourcepoor settings.7 HIV transmission from mother to child can occur antenatally (in utero), during the intrapartum period and postnatally (through breastfeeding). The absolute risk of these modes of transmission has been estimated at 510%, 1020% and 530%, respectively.8 It is important to differentiate between modes of transmission, as these inform prevention strategies. Please see Table 1 for a summary of estimated risks of transmission by population and intervention. All infants born to HIV-positive mothers have serum HIV antibodies because of passive placental transfer, which persist up to 18 months of age; this does not indicate infection with the virus. A positive HIV DNA on polymerase chain reaction testing from the infant before 7 days of age indicates in utero transmission; if positive at 1 month this indicates intrapartum transmission, although the cut-offs are not absolute.9 The risk factors associated with HIV transmission are well documented (see Box 1). There is a strong positive correlation between maternal antenatal viral load and the risk of both in utero and intrapartum transmission;10 interventions to reduce maternal viral load reduce HIV transmission risk. Duration of ruptured membranes has been associated with intrapartum transmission in previous research,9, 11 although new UK data show that this may not be the case for women on effective highly active antiretroviral therapy (HAART) with undetectable viral loads.12

The team will give the positive HIV result, manage the pregnancy, delivery and care of the infant and support the woman and her family through what is often a traumatic time.

Antenatal HIV testing

Early detection of antenatal HIV infection ensures that pregnancy and delivery, as well as infant feeding options, can be managed to minimise the risk of vertical HIV transmission. Antenatal HIV screening also helps to ensure that HIV-negative women can protect themselves against acquiring the virus. One of the successes in the UK has been the normalisation of HIV testing as part of routine investigations undertaken during pregnancy. The British HIV Association (BHIVA) guideline on HIV testing recommends universal opt-out testing in both antenatal and pregnancy termination services;13 the HIV test is done along with routine booking blood tests unless the woman specifically declines it. The guideline states that it should be within the competence of any doctor, midwife, nurse or trained healthcare worker to obtain consent for and conduct an HIV test. Before the adoption of universal opt-out HIV testing in antenatal clinics, only a third of HIV-positive pregnant women were diagnosed by delivery and most of these had already been diagnosed prior to conception.14 The latest Health Protection Agency figures from 2009 show that the uptake of antenatal HIV testing in the UK is around 95%.15 International guidance recommends that HIV testing and counselling is offered to all women attending antenatal, delivery and postnatal services in generalised HIV epidemics.16 Global figures for the uptake of antenatal testing are less encouraging than those in the UK, although they are improving. In 2010 only 35% of women giving birth in low or middle-income countries received an HIV test, up from 15% in 2007. In sub-Saharan Africa, the corresponding percentage increase was from 17% to 42%.1 The rise in provider-initiated, rapid point-of-care tests (which do not require laboratory processing) has been instrumental in increasing the uptake of HIV testing among pregnant women in areas of high HIV prevalence.5 Barriers to HIV testing in these settings are multitudinous and include:

The multidisciplinary approach

HIV-positive pregnant women are best managed by a multidisciplinary team. This may include a specialist midwife, HIV (or infectious disease) physician, an obstetrician with an interest in HIV, a paediatrician, an HIV community nurse specialist and a pharmacist. This team is responsible both for women with known HIV and those who are newly diagnosed.

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Table 1. Estimated risk of vertical HIV transmission by population and intervention6, 8, 22, 23, 30, 3645, 50, 51 Estimated risk of vertical vertical transmission (%) 2045 1530 6.48.2 12.218 4.19.4 0.56 1 0.1

Population Resource-poor, breastfeeding Resource-poor, non-breastfeeding Resource-rich, non-breastfeeding Resource-poor, breastfeeding Resource-poor, non-breastfeeding Resource-poor, breastfeeding Resource-rich, non-breastfeeding Resource-rich, non-breastfeeding

Intervention None None Elective caesarean section Daily AZT Daily AZT Maternal HAART to 6 months postnatal +/- infant prophylaxis HAART HAART Maternal viral load <50 copies/ml at 36 weeks

These gures are a guide only, based on a review of the relevant literature. AZT = zidovudine; HAART = highly active antiretroviral therapy

lack of health system infrastructure; financial impediments; and social and cultural barriers, including the persistent stigma still attached to the diagnosis of HIV.17 In high-prevalence areas women are more at risk of acquiring primary HIV infection during pregnancy.18 Primary HIV infection is associated with high plasma HIV RNA levels, which increases the risk of mother to child transmission. Some countries, such as South Africa, therefore, have adopted a policy of re-testing pregnant women in the third trimester.19 Serodiscordant couples (in which one partner is initially HIVnegative and the other positive) may account for upwards of 60% of HIV infections in high-prevalence settings in Africa.20 Voluntary testing and counselling of cohabiting couples increases safer sex practices and disclosure of HIV status.21 Testing in the antenatal setting provides an opportunity to offer testing to male partners and for safe sex promotion for serodiscordant couples, in both resource-poor and resourcerich countries.

Table 2. Maternal drug strategies for prevention of mother to child transmission of HIV in the UK (adapted from BHIVA guidelines, 200823 ) Maternal CD4 count (cells/l) <350 Maternal viral load <600010 000 copies/ml HAART >350 START or zidovudine monotherapy + elective caesarean section START

Maternal viral load >10 000 copies/ml

HAART

HAART = highly active antiretroviral therapy; START = short-term antiretroviral therapy

Antiretroviral therapy
HAART has revolutionised the management of HIV and is the single most important intervention in reducing mother to child transmission in pregnant women. Suppression of maternal HIV viral load improves maternal health outcomes and prevents both in utero, intrapartum and postnatal transmission. Most pregnant HIV-positive women require triple drug therapy, whether initiated for their own health and continued for the rest of their life, or given as a short course to prevent mother to child transmission during the antenatal and postnatal periods. Decisions about maternal antiretroviral therapy and mode of delivery in the UK are based on maternal viral load, but this is often unavailable in resource-poor countries. The BHIVA and the WHO guidelines differentiate pregnant women into those who require HAART for their own health and those who do not.22, 23 The threshold

for starting lifelong HAART has been revised to a CD4 count <350 cells/l. Different treatment strategies are summarised in Table 2 and Table 3. In women who require HAART for their own health, BHIVA recommends that they are treated with a nucleoside reverse transcriptase inhibitor (NRTI) backbone of zidovudine and lamivudine, together with a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor, because this combination has been used most widely in pregnant women.23 However, non-zidovudine-based HAART is increasingly being used in women pre and post-conception and so far there is no evidence of increased risk of maternal HIV viral load at delivery, congenital abnormality or mother to child transmission.24 The WHO guideline also recommends zidovudine and lamivudine as the NRTI backbone, but with nevirapine or efavirenz22 (protease inhibitors are considerably more expensive than NNRTIs and are not widely available in resource-limited countries). In the UK, women who do not require HAART for their own health have two options. Short-term antiretroviral therapy

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HIV in pregnancy: an international perspective

Table 3. Maternal drug strategies for prevention of mother to child transmission of HIV in resource-limited countries (adapted from WHO guidelines, 201022 ) Maternal CD4 count (cells/l) <350 (or WHO clinical stages 3 and 4 if CD4 count unavailable) HAART >350 (or WHO clinical stages 1 and 2 if CD4 count unavailable) Option A: Daily antepartum AZT Single dose nevirapine at onset of labour AZT + 3TC during labour and delivery AZT + 3TC for 7 days postpartum Option B: START: commence at 14 weeks and continue until 1 week after end of breast milk exposure

AZT = zidovudine; HAART = highly active antiretroviral therapy; START = short-term antretroviral therapy; 3TC = lamivudine

(START) is a three-drug regimen initiated in the second trimester and discontinued at delivery. UK guidelines suggest a protease inhibitor-based regimen, with a high genetic barrier to resistance and shorter half-life compared with NNRTIs, which minimises the risk of developing drug resistance. Recent data suggest that in women with a plasma viral load >10 000 copies per ml, START may need to be initiated before 20 weeks to achieve an undetectable viral load at delivery.25 If the maternal HIV viral load is <600010 000 copies per ml and the woman does not wish to take START, daily zidovudine initiated at 2428 weeks with an elective caesarean section at 38 weeks is an option.23 This approach minimises the risk of fetal and maternal toxicity and is associated with a <1% risk of transmission.6 The most recent WHO guideline also suggests that women with a CD4 count >350 cells/l can have zidovudine monotherapy.22 See Table 4 for examples of antiretroviral regimens.

The effectiveness of antiretroviral therapy has to be considered alongside potential maternal and fetal toxicity. There are many ethical and practical barriers to conducting trials in pregnant women, but there are over 15 years of experience of antiretroviral therapy in pregnancy and good data on safety and efficacy. Potential pregnancy-specific maternal adverse effects include mitochondrial toxicity with older NRTIs (which are no longer recommended) and a possible increased risk of glucose intolerance with protease inhibitors. Nevirapine is widely used in pregnancy worldwide but can cause rashes and hepatotoxicity; this occurs more frequently in women with a CD4 count >250 cells/l.23 There are conflicting data on whether HAART is associated with preterm delivery26, 27 and research is ongoing. Recent data from the UK and the Republic of Ireland suggest that for every 100 HIV transmissions prevented by HAART, there may be 63 additional preterm deliveries, including 23 at <32 weeks of gestation.28

Table 4. Examples of antiretroviral therapy regimens in pregnancy (adapted from BHIVA and WHO guidelines22, 23 ) BHIVA guidelines Backbone: 2 NRTIs, e.g. tenofovir + emtricitabine or AZT + 3TC Plus: boosted protease inhibitor, e.g. LPV/r, ATZ/r or DRV/r WHO guidelines Backbone: 2 NRTIs, e.g. AZT + 3TC, tenofovir + emtricitabine Plus either: boosted protease inhibitor, e.g. LPV/r Or: NNRTI, e.g. efavirenz Alternative regimen: 3 NRTIs, e.g. AZT + 3TC + abacavir Backbone: 2 NRTIs, e.g. AZT + 3TC, TVF + emtricitabine Plus: NNRTI, e.g. nevirapine or efavirenz

START

HAART

Backbone: 2 NRTIs, e.g. tenofovir + emtricitabine, AZT + 3TC Plus either: NNRTI, e.g. efavirenz , nevirapine (if CD4 <250 cells/l) Or: boosted protease inhibitor, e.g. LPV/r, ATZ/r or DRV/r

AZT = zidovudine; ATZ/r = atazanavir boosted with ritonavir; DRV/r = darunavir boosted with ritonavir; HAART = highly active antiretroviral therapy; LPV/r = lopinavir boosted with ritonavir; NRTI = nucleoside reverse transcriptase inhibitor; START = short-term antiretroviral therapy; 3TC = lamivudine

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There is a theoretical concern that NRTIs could cause mitochondrial toxicity in infants exposed perinatally, but there is limited evidence and further research in this area is required. The Antiretroviral Pregnancy Registry has found no increase in overall risk of birth defects in infants exposed to antiretroviral therapy, including efavirenz, in the first trimester,29 although additional prospective data is required to confirm this.

Infant feeding
Postnatal transmission of HIV occurs due to breastfeeding. Breast milk from HIV-infected mothers contains cell-free HIV RNA and intracellular HIV DNA and both are thought to contribute to transmission.34 The breast milk viral load correlates with the plasma viral load.35 In breastfeeding populations, 2444% of all mother to child transmission of HIV is due to breastfeeding and the cumulative probability of HIV transmission is fairly constant over time and so correlates with duration of breastfeeding.36, 37 Transmission risk is highest with mixed feeding compared with exclusive breast or bottle feeding36, 38 and complete replacement of infant feeding with formula reduces postnatal transmission. Several studies in the developing world show that maternal HAART (or START continued through the breastfeeding period) to suppress maternal viral load and for infant prophylaxis significantly reduces the rate of postnatal transmission of HIV.3945 The estimated cumulative probability of postnatal transmission of HIV in these cohorts is 0.53% at 69 months of age.39, 4244 Breastfeeding reduces infant morbidity and mortality, protects against childhood infections and promotes child spacing. In resource-poor countries mothers often have no access to clean water or formula for safe replacement feeding. Moreover, there can be a stigma attached to replacement feeding, as it can be seen as an indication of HIV infection in both resource-poor and resource-rich countries.41 WHO only advocates replacement feeding if it is acceptable, feasible, affordable, safe and sustainable and recommends that, where this is not the case, women who are HIV-positive breastfeed their infant exclusively until the age of 6 months, then introduce complementary foods and continue breastfeeding until the age of 12 months.46 Mothers who are not eligible for HAART should continue START until all breastfeeding has ceased if resources allow and antiretroviral prophylaxis is recommended for the infant depending on the maternal treatment strategy.22 In the UK exclusive replacement feeding is possible because women have access to formula, clean water, sterilising equipment, counselling and support from postnatal services. There is concern about the unknown risk of exposing uninfected breastfeeding infants to antiretroviral therapy, either through maternal HAART or infant prophylaxis, and the potential for development of viral resistance in HIV-infected infants exposed to antiretroviral therapy who have yet to be diagnosed. This may be a priority in countries where support for formula feeding is readily available. The under-reporting of mixed feeding practices in those encouraged to formula feed is also a concern, as there is no evidence on the risk of transmission with mixed feeding from mothers on HAART. BHIVA and the Childrens HIV Association recently issued guidance, in which they continue to recommend that mothers

Management of labour and delivery

In women with HIV this has evolved as understanding of the risks of intrapartum transmission has improved. In the 1990s, prior to the advent of HAART, elective caesarean section was found to reduce intrapartum mother to child transmission of HIV.30 In the UK the rate of mother to child transmission of HIV in women on HAART is 0.7% with both elective caesarean section and vaginal delivery.6 The potentially decreased risk of mother to child transmission by elective caesarean section in women with higher viral loads, may be outweighed by the increased risk of complications to both mother and infant. The risks associated with vaginal birth after caesarean section also need to be considered, if the woman is likely to have subsequent children. If the maternal viral load is undetectable at 36 weeks, therefore, a vaginal delivery can be planned. Women on zidovudine monotherapy and those on HAART (or START) with a detectable viral load at 36 weeks (>400 copies per ml) are recommended to have elective caesarean section at 38 weeks. A caesarean section should be considered in those with a viral load 50400 copies per ml.31 Prelabour rupture of membranes is associated with increased risk of HIV transmission, so delivery should be expedited if the woman is more than 34 weeks pregnant. Prior to 34 weeks, obstetric management should take into account the risk of neonatal morbidity and mortality associated with prematurity, as well as other factors such as maternal HAART, viral load and the presence of comorbidities.23 The decision to deliver should include the paediatrician, HIV-specialist physician and the obstetrician. In many low and middle-income countries, elective caesarean section is often not a feasible option. In the less and least developed areas of the world, the proportion of births attended by a skilled health worker is 62% and 35%, respectively. The rate of caesarean section in sub-Saharan Africa is thought to be 3.66.5%,32 compared with 24.8% in 2009 in England and Wales.33 Invasive procedures that could theoretically increase the risk of transmission during labour, such as fetal blood sampling, should be avoided if possible. There is no evidence that washing the infant in chlorhexidine after delivery reduces transmission; the infant should be wiped clean and only washed once warm.

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HIV in pregnancy: an international perspective

known to be HIV-positive refrain from breastfeeding from birth.47

Conclusion
At the United Nations Millennium Summit in 2000, 189 world leaders agreed to meet the Millennium Development Goals. These include: halting the spread of HIV/AIDS, achieving universal access to treatment of HIV/AIDS to those who need it, reducing the under-5s mortality rate by two-thirds and reducing the maternal mortality ratio by two-thirds, by 2015. In June 2011, the Countdown to Zero: Global Plan Towards the Elimination of New HIV Infections in Children by 2015 and Keeping their Mothers Alive set ambitious goals to reduce new childhood infections by 90%, and HIV-related maternal deaths by 50%.48 There has been considerable success in some areas: the coverage of antiretroviral treatment in poorer countries has increased four-fold over 5 years, there has been the first decline in the death rate from AIDS and there has been a significant increase in the proportion of pregnant HIV-positive women getting antiretroviral therapy to prevent mother to child transmission.5, 49 Nevertheless, we are still falling well short of the targets and the HIV/AIDS epidemic remains a global health emergency, with a significant impact on maternal and child mortality and morbidity. Experience in the UK and other resource-rich countries has shown that a universal antenatal HIV screening programme, with appropriate and timely interventions for HIV-positive women, can reduce the risk of mother to child transmission of HIV to very low levels. The challenge of implementing this strategy worldwide is considerable: without access to specialist antenatal care, low-cost drugs and support for exclusive breast or formula feeding, HIV-positive women in the developing world will continue to transmit the virus to their children.

References
1 Joint United Nations Programme on HIV/AIDS (UNAIDS) and World Health Organization (WHO). Global HIV/AIDS Response: Epidemic Update and Health Sector Progress Towards Universal Access 2011. Geneva: WHO, 2011 [whqlibdoc.who.int/ publications/2011/9789241502986_eng.pdf]. 2 Hogan MC, Foreman KJ, Naghavi M, Ahn SY, Wang M, et al. Maternal mortality for 181 countries, 19802008: a systematic analysis of progress towards Millennium Development Goal 5. Lancet 2010;375:160923 [http://dx.doi.org/10.1016/S0140-6736(10) 60518-1]. 3 World Health Organization. PMTCT Strategic Vision 20102015: Preventing Mother-to-Child Transmission of HIV to Reach the UNGASS and Millennium Development Goals. Geneva: WHO; 2010 [www.who.int/hiv/pub/mtct/strategic_vision.pdf]. 4 World Health Organization. Antenatal Care in Developing Countries: Promises, Achievements and Missed Opportunities. An Analysis of Trends, Levels and Differentials 19902001. Geneva: WHO; 2003 [http://whqlibdoc.who.int/publications/2003/9241590947.pdf].

5 World Health Organization. Towards Universal Access: Scaling up Priority HIV/AIDS Interventions in the Health Sector. Progress Report 2010. Geneva: WHO; 2010 [www.unicef.org/eapro/ Towards_Universal_Access_on_HIVAIDS.pdf]. 6 Townsend CL, Cortina-Borja M, Peckham CS, de Ruiter A, Lyall H, et al. Low rates of mother-to-child transmission of HIV following effective pregnancy interventions in the United Kingdom and Ireland, 20002006. AIDS 2008;22:97381 [http://dx.doi.org/ 10.1097/QAD.0b013e3282f9b67a]. 7 Wiktor SZ, Ekpini E, Nduati RW. Prevention of mother-to-child transmission of HIV-1 in Africa. AIDS 1997;11 (Suppl B):S79 87. 8 De Cock KM, Fowler MG, Mercier E, de Vincenzi I, Saba J, et al. Prevention of mother-to-child HIV transmission in resourcepoor countries: translating research into policy and practice. JAMA 2000;283:117582 [http://dx.doi.org/10.1001/jama.283.9.1175]. 9 Magder LS, Mofenson L, Paul ME, Zorrilla CD, Blattner WA, et al. Risk factors for in utero and intrapartum transmission of HIV. J Acquir Immune Dec Syndr 2005;38:8795 [http://dx.doi.org/10.1097/00126334-200501010-00016]. 10 Garcia PM, Kalish LA, Pitt J, Minkoff H, Quinn TC, et al. Maternal levels of plasma human immunodeciency virus type 1 RNA and the risk of perinatal transmission. N Engl J Med 1999;341:394402 [http://dx.doi.org/10.1056/NEJM199908053410602]. 11 International Perinatal HIV Group. Duration of ruptured membranes and vertical transmission of HIV-1: a meta-analysis from 15 prospective cohort studies. AIDS 2001;15:35768 [http://dx.doi.org/10.1097/00002030-200102160-00009]. 12 Haile-Selassie H, Tookey P, de Ruiter A. Duration of ruptured membranes and vertical transmission of HIV: data from national surveillance in the UK and Ireland. Second Joint Conference of the British HIV Association and the British Association for Sexual Health and HIV. Manchester, 2010. Abstract 02. HIV Medicine 2010;11(Suppl 1):1119 [www.bhiva.org/documents/Conferences/ Manchester2010/Abstracts10Entire.pdf]. 13 British HIV Association, British Association of Sexual Health and HIV, British Infection Society. UK National Guidelines for HIV Testing 2008. London: BHIVA; 2008. 14 Royal College of Paediatrics and Child Health. Reducing Mother to Child Transmission of HIV Infection in the United Kingdom. Update Report of an Intercollegiate Working Party. London: RCPCH; 2006 [www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1197382224430]. 15 Health Protection Agency. HIV in the United Kingdom: 2009 Report. London: HPA; 2009 [www.hpa.org.uk/ webc/HPAwebFile/HPAweb_C/1259151891830]. 16 World Health Organization, UNAIDS. Guidance on Provider-initiated HIV Testing and Counselling in Health Facilities. Geneva: WHO; 2007 [www.who.int/hiv/pub/guidelines/9789241595568_en.pdf]. 17 Sambisa W, Curtis S, Mishra V. AIDS stigma as an obstacle to uptake of HIV testing: evidence from a Zimbabwean national population-based survey. AIDS Care 2010;22:17086 [http://dx.doi.org/10.1080/09540120903038374]. 18 Moodley D, Esterhuizen TM, Pather T, Chetty V, Ngaleka L. High HIV incidence during pregnancy: compelling reason for repeat HIV testing. AIDS 2009;23:12559 [http://dx.doi.org/ 10.1097/QAD.0b013e32832a5934]. 19 Soorapanth S, Sansom S, Bulterys M, Besser M, Theron G, Fowler MG. Cost-effectiveness of HIV rescreening during late pregnancy to prevent mother-to-child HIV transmission in South Africa and other resource-limited settings. J Acquir Immune Dec Syndr 2006;42:213 21 [http://dx.doi.org/10.1097/01.qai.0000214812.72916.bc]. 20 Bishop M, Foreit K. Serodiscordant Couples in Sub-Saharan Africa: What Do Survey Data Tell Us? Washington DC: Futures Group, Health Policy Initiative, Task Order 1; 2010 [www.health policyinitiative.com/Publications/Documents/1070_1_Serodiscordant_ Couples_FINAL_3_04_10_acc.pdf].

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Byrne et al.

21 Dunkle KL, Stephenson R, Karita E, Chomba E, Kayitenkore K, et al. New heterosexually transmitted HIV infections in married or cohabiting couples in urban Zambia and Rwanda: an analysis of survey and clinical data. Lancet 2008;371:218391 [http://dx.doi.org/10.1016/S0140-6736(08)60953-8]. 22 World Health Organization. Antiretroviral Drugs for Treating Pregnant Women and Preventing HIV Infection in Infants: Recommendations for a Public Health Approach. Geneva: WHO; 2010 [http://whqlibdoc.who.int/publications/2010/9789241599818_eng. pdf]. 23 de Ruiter A, Mercey D, Anderson J, Chakraborty R, Clayden P, et al. British HIV Association and Childrens HIV Association guidelines for the management of HIV infection in pregnant women 2008. HIV Med 2008;9:452502 [http://dx.doi.org/10.1111/j.14681293.2008.00619.x]. 24 Tariq S, Townsend CL, Cortina-Borja M, Duong T, Elford J, Thorne C, et al; European Collaborative Study; National Study of HIV in Pregnancy Childhood. Use of zidovudine-sparing HAART in pregnant HIV-infected women in Europe: 20002009. J Acquir Immune Dec Syndr 2011;57:32633 [http://dx.doi.org/10.1097/ QAI.0b013e31821d34d0]. 25 Read PJ, Khan P, Mandalia S, Naftalin C, Harrisson U, et al. When should HAART be initiated in pregnancy to achieve an undetectable viral load? [Poster.] 17th Conference on Retroviruses and Opportunistic Infections. San Francisco, 2010 [www.retroconference.org/2010/PDFs/896.pdf]. 26 European Collaborative Study. HIV-infected pregnant women and vertical transmission in Europe since 1986. AIDS 2001;15:76170 [http://dx.doi.org/10.1097/00002030-200104130-00012]. 27 Patel K, Shapiro DE, Brogly SB, Livingston EG, Stek AM, et al; P1025 team of the International Maternal Pediatric Adolescent AIDS Clinical Trials Group.Prenatal protease inhibitor use and risk of preterm birth among HIV-infected women initiating antiretroviral drugs during pregnancy. J Infect Dis 2010;201:1035 44 [http://dx.doi.org/10.1086/651232]. 28 Townsend CL, Tookey PA, Newell ML, Cortina-Borja M. Antiretroviral therapy in pregnancy: balancing the risk of preterm delivery with prevention of mother-to-child HIV transmission. Antivir Ther 2010;15:77583 [http://dx.doi.org/10.3851/IMP1613]. 29 Antiretroviral Pregnancy Registry Steering Committee. Antiretroviral Pregnancy Registry International Interim Report for 1 January 1989 through 31 January 2011. Wilmington, NC: Registry Coordinating Center; 2011 [www.apregistry.com/forms/interim_report.pdf]. 30 Read JS, Newell MK. Efcacy and safety of cesarean delivery for prevention of mother-to-child transmission of HIV-1. Cochrane Database Syst Rev 2005;(4):CD005479. 31 National Institute for Health and Clinical Excellence. NICE Guidance on Caesarean Section. London: National Institute for Health and Clinical Excellence; 2011 [www.nice.org.uk/nicemedia/ live/13620/57163/57163.pdf]. 32 Dumont A, de Bernis L, Bouvier-olle M, Br eart G; MOMA Study Group. Caesarean section rate for maternal indication in subSaharan Africa: a systematic review. Lancet 2001;358:132833 [http://dx.doi.org/10.1016/S0140-6736(01)06414-5]. 33 HES Online Hospital Episode Statistics. Maternity Data. NHS Maternity Statistics, 200910 [www.hesonline.nhs. uk/Ease/servlet/ContentServer?siteID = 1937&categoryID = 1475]. 34 Lehman DA, Chung MH, John-Stewart GC, Richardson BA, Kiarie J, et al. HIV-1 persists in breast milk cells despite antiretroviral treatment to prevent mother-to-child transmission. AIDS 2008;22:147585 [http://dx.doi.org/10.1097/QAD.0b013e328302cc11]. 35 Pillay K, Coutsoudis A, York D, Kuhn L, Coovadia HM. Cell-free virus in breast milk of HIV-1-seropositive women. J Acquir Immune Dec Syndr 2000;24:3306. 36 Nduati R, John G, Mbori-Ngacha D, Richardson B, Overbaugh J,

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et al. Effect of breastfeeding and formula feeding on transmission of HIV-1: a randomized clinical trial. JAMA 2000;283:116774 [http://dx.doi.org/10.1001/jama.283.9.1167]. Coutsoudis A, Dabis F, Fawzi W, Gaillard P, Haverkamp G, et al. Late postnatal transmission of HIV-1 in breast-fed children: an individual patient data meta-analysis. J Infect Dis 2004;189:215466 [http://dx.doi.org/10.1086/420834]. Coovadia HM, Rollins NC, Bland RM, Little K, Coutsoudis A, et al. Mother-to-child transmission of HIV-1 infection during exclusive breastfeeding in the rst 6 months of life: an intervention cohort study. Lancet 2007;369:110716 [http://dx.doi.org/10.1016/S0140-6736(07)60283-9]. Peltier CA, Ndayisaba GF, Lepage P, van Griensven J, Leroy V, et al. Breastfeeding with maternal antiretroviral therapy or formula feeding to prevent HIV postnatal mother-to-child transmission in Rwanda. AIDS 2009;23:241523. Marazzi MC, Nielsen-Saines K, Buonomo E, Scarcella P, Germano P, et al. Increased infant human immunodeciency virus-type one free survival at one year of age in sub-Saharan Africa with maternal use of highly active antiretroviral therapy during breast-feeding. Pediatric Infect Dis J 2009;28:4837 [http://dx.doi.org/10.1097/INF. 0b013e3181950c56]. Horvath T, Madi BC, Iuppa IM, Kennedy GE, Rutherford G, et al. Interventions for preventing late postnatal mother-to-child transmission of HIV. Cochrane Database Syst Rev 2009;(1):CD006734 [http://dx.doi.org/10.1097/QAI.0b013e3181b323ff]. Shapiro R. A randomized trial comparing highly active antiretroviral therapy regimens for virologic efcacy and the prevention of mother-to-child HIV transmission among breastfeeding women in Botswana (The Mma Bana Study). [Abstract.] 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention, 1922 July 2009, Cape Town, South Africa [www.ias2009.org/pag/Abstracts.aspx ?SID=2435&AID=3821]. Kilewo C, Karlsson K, Ngarina M, Massawe A, Lyamuya E, et al. Prevention of mother-to-child transmission of HIV-1 through breastfeeding by treating mothers with triple antiretroviral therapy in Dar es Salaam, Tanzania: the Mitra Plus study. J Acquir Immune Dec Syndr 2009;52:40616. Chasela C, Hudgens M, Jamieson D, Kayira D, Hosseinipour M, et al. Both maternal HAART and daily infant nevirapine (NVP) are effective in reducing HIV-1 transmission during breastfeeding in a randomized trial in Malawi: 28 week results of the Breastfeeding, Antiretroviral and Nutrition (BAN) Study. 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention, 1922 July 2009, Cape Town, South Africa. Abstract no. WELBC103 [www.iasociety.org/Default.aspx?pageId = 11&abstractId = 200722774%20]. Kesho Bora Study Group, de Vincenzi L. Triple antiretroviral compared with zidovudine and single-dose nevirapine prophylaxis during pregnancy and breastfeeding for prevention of mother-to-child transmission of HIV-1 (Kesho Bora study): a randomised controlled trial. Lancet Infect Dis 2011;11:17180 [http://dx.doi.org/10.1016/S1473-3099(10)70288-7]. World Health Organization. Guidelines on HIV and Infant Feeding. 2010. Principles and Recommendations for Infant Feeding in the Context of HIV and a Summary of Evidence. Geneva: WHO; 2010 [www.who.int/child_adolescent_health/documents/9789241 599535/en/]. British HIV Association and Childrens HIV Association. Position Statement on HIV and Infant Feeding in the UK. London: BHIVA; 2010 [www.bhiva.org/BHIVA-CHIVA-PositionStatement.aspx]. UNAIDS. Countdown to Zero: Global Plan Towards the Elimination of New HIV Infections in Children by 2015 and Keeping their Mothers Alive. Geneva: UNAIDS; 2011 [www.unaids.org/en/media/unaids/ contentassets/documents/unaidspublication/2011/20110609_JC2137 _Global-Plan-Elimination-HIV-Children_en.pdf].

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49 United Nations. The Millennium Development Goals Report, 2011. New York: United Nations; 2011 [www.un.org/millenniumgoals/ pdf/(2011_E)%20MDG%20Report%202011_Book%20LR.pdf]. 50 International Perinatal HIV Group. The mode of delivery and the risk of vertical transmission of human immunodeciency virus type 1 a meta-analysis of 15 prospective cohort studies.

New Engl J Med 1999;340:97787 [http://dx.doi.org/10.1056/ NEJM199904013401301]. 51 European Mode of Delivery Study Group. Elective caesareansection versus vaginal delivery in prevention of vertical HIV-1 transmission: a randomised clinical trial. Lancet 1999;353:10359 [http://dx.doi.org/10.1016/S0140-6736(98)08084-2].

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